The renin-angiotensin-aldosterone system (RAAS) is a complex network that regulates blood pressure and fluid volume. This review discusses the evolution of the RAAS, its role in cardiovascular health and kidney disease, and the development of novel medications. The RAAS has been a survival trait for humans, but its overactivity in modern diets has led to hypertension and cardiovascular risk. RAAS inhibitors, such as ACE inhibitors and ARBs, have been effective in reducing these risks, but their complete inhibition can cause adverse effects. New drugs, including ARNIs, non-steroidal MRAs, and aldosterone synthase inhibitors, offer additional benefits and potential improvements in treatment. However, the optimal combination of these drugs to achieve maximum renal and cardiovascular protection while minimizing side effects remains a challenge. Personalized therapy, considering individual patient characteristics and biomarkers, may be the future of RAAS inhibition.The renin-angiotensin-aldosterone system (RAAS) is a complex network that regulates blood pressure and fluid volume. This review discusses the evolution of the RAAS, its role in cardiovascular health and kidney disease, and the development of novel medications. The RAAS has been a survival trait for humans, but its overactivity in modern diets has led to hypertension and cardiovascular risk. RAAS inhibitors, such as ACE inhibitors and ARBs, have been effective in reducing these risks, but their complete inhibition can cause adverse effects. New drugs, including ARNIs, non-steroidal MRAs, and aldosterone synthase inhibitors, offer additional benefits and potential improvements in treatment. However, the optimal combination of these drugs to achieve maximum renal and cardiovascular protection while minimizing side effects remains a challenge. Personalized therapy, considering individual patient characteristics and biomarkers, may be the future of RAAS inhibition.